An experimental plan is proposed for examining the intrinsic neural mechanisms that influence mucosal functions in human large intestine. The overall aim of the project is threefold. The first is to establish basal rates of absorption and secretion of ions and to investigate the mechanisms that are involved in these transport processes. The second is to analyze the effects of activation of enteric nerves on colonic mucosal function; and the third is to identify the types of enteric nerves and neurotransmitter substances that mediate neuronal influences on the large intestinal mucosa. The studies will be done on flat sheet preparations of surgically resected human large intestine in vitro. The basic approach will be to mount the tissues in Ussing type flux chambers that are modified for electrical field stimulation of intramural neurons and to measure and evaluate changes in short-circuit currents and ionic fluxes that are evoked or modified by electrical activation of intramural nerves. Pharmacological analysis and assays for putative neurotransmitter substances that are released into the organ bath by electrical field stimulation will be the principal methods for identifying the types of nerves that influence the mucosa. The project will bypass animal models and provide definitive information on functional relationships between the enteric nervous system and the mucosal epithelium in the human large intestine. It is expected to yield new information on basic function that is needed for better understanding of the abnormal secretory and absorptive mucosal processes that underlie constipation and diarrheal states in humans.